N-terminal domain of complexin independently activates calcium-triggered fusion

作者：Lai Ying; Choi Ucheor B; Zhang Yunxiang; Zhao Minglei; Pfuetzner Richard A; Wang Austin L; Diao Jiajie; Brunger Axel T

来源：Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(32): E4698-E4707.

DOI：10.1073/pnas.1604348113

• synaptic vesicle fusion
• SNAREs
• synaptotagmin
• membrane fusion
• virus fusion

Complexin activates Ca2+-triggered neurotransmitter release and regulates spontaneous release in the presynaptic terminal by cooperating with the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and the Ca2+-sensor synaptotagmin. The N-terminal domain of complexin is important for activation, but its molecular mechanism is still poorly understood. Here, we observed that a split pair of N-terminal and central domain fragments of complexin is sufficient to activate Ca2+-triggered release using a reconstituted single-vesicle fusion assay, suggesting that the N-terminal domain acts as an independent module within the synaptic fusion machinery. The N-terminal domain can also interact independently with membranes, which is enhanced by a cooperative interaction with the neuronal SNARE complex. We show by mutagenesis that membrane binding of the N-terminal domain is essential for activation of Ca2+-triggered fusion. Consistent with the membrane-binding property, the N-terminal domain can be substituted by the influenza virus hemagglutinin fusion peptide, and this chimera also activates Ca2+-triggered fusion. Membrane binding of the N-terminal domain of complexin therefore cooperates with the other fusogenic elements of the synaptic fusion machinery during Ca2+-triggered release.

• 出版日期2016-8-9